Drugs—chemical substances used or intended to be used to modify or explore the physiological condition or pathological state for the benefit of the recipient. Drugs may be used for prevention, diagnosis and treatment.

Major divisions of pharmacology—

1. Pharmacokinetics.

2. Pharmacodynamics.

Other divisions—

1. Pharmacotherapeutics.

2. Clinical pharmacology.

3. Pharmacogenetics

4. Immunopharmacology

5. Pharmacognosy

6. Toxicology

7. Pharmacopoeia

Pharmacokinetics—(what the body does to the drug)—it is the branch of pharmacology that deals with drug dose, routes of administration and absorption, distribution, metabolism and excretion.

Pharmacodynamics—(what the drug does to the body)—it is a branch of pharmacology that deals with the mechanism of action, pharmacological effects, indication and contraindication of use and adverse effects of drugs.

Toxicology—it is the branch of pharmacology which deals with poisonous drugs, their source, properties, sign-symptoms they produce and management of poisoning.

Pharmacopoeia—it is a book published by authority of recognized body which contains the list of drug, their properties, description, preparation and method of prescribing.

Pharmacogenetics—it is that branch of pharmacology which deals with genetic variations in the drug response.

Ex—

§ Isoniazid is an anti-tubercular drug which is metabolized by acetylation. If acetylation process is increased by that person for the genetic factor then more drug is needed.

§ Patients with glucose-6-phosphate dehydrogenase deficiency may produce haemolytic anaemia if anti-malarial drug is given

To learn the overview of psychopharmacology in accordance with current observations with the underlying premise of the patients basic Bill of "Rights". That is for the practitioner to get the right drug to the right patient at the right time for the right condition with a a minimum of adverse effects.

With the "Bill of Rights" comes patient safety, discontinuation syndrome, compliance, stigma. We will address DS to start and ultimately all 3 of these topics as they apply to psychopharmacology, under the umbrella and auspices of Patient Safety.Joel Lamoure 21:53, 17 March 2007 (UTC)

The vast majority of adverse psychiatric drug reactions are of Type A in that they are dose-dependent or recognizably related to the known pharmacological properties of the drug. These could tritely be labelled as "Anticipated" reactions. the Type B reactions are those that encompass immunological like reactions, such as anaphylaxis demonstrated from penicllin class agents.

**Please note that the newer atypical agents have a far lower propensity to cause movement disorders. Risperidone over 6mg/day is linked with increased EPS however.
Atypical Antipsychotics have their own unique side effect profiles that include metabolic changes, prolactin alterations and fluctuations in the patients sugars and cholesterol values.

Understanding discontinuation syndrome (DS) and becoming familiar with the medications that cause it are important issues in the treatment of patients with mental health conditions. The purpose of this article is to enhance the awareness of the potential that your patients may be experiencing DS. There is a challenge in this field, in that the symptoms of DS in the medications that will be explored in this article often mimics the initial condition for which they were employed. Even with antidepressants, only 72% of psychiatrists and 30% of GPs were aware that patients might experience DS. (1)

What is DS?

Discontinuation Syndrome (DS) is a condition where the patient experiences adverse effects that result from an abrupt discontinuation of the medication. Symptoms of DS begin to appear generally within the first 24-48 hours after drug discontinuation or dose reduction and last for up to 7-14 days depending on the medication. (2) Also, some adverse effects from discontinuation may persist from months after, as seen with paroxetine. Symptoms of DS are distinct from relapse of underlying disease and will resolve after drug reinstitution, but as alluded to, often mimic or appear to be a relapse of the initial mental health condition (2,3). In this article, we will address tricyclic antidepressants, atypical antipsychotics and benzodiazepines. There are discontinuation syndromes seen also with a myriad of agents including beta blockers (eg propranolol) and narcotics/ opiates, which will not be addressed herein. It becomes an issue for practitioners as inherently patients in mental health are not compliant, due to cost, adverse effects or stigma and also in medical situations where there is a decision to hold medications (e.g. pre and post-operatively). (4)

There are three classes of drugs implicated in DS we will cover in this subsection:

Selective serotonin reuptake inhibitors (SSRI)/ Serotonin-nor epinephrine reuptake inhibitor •(SNRI) agents. Although these agents are the cornerstones of therapy for depression, abrupt discontinuation may lead to major adverse reactions, as we shall visit.

•Antipsychotics (E.g.: Olanzapine, Quetiapine, Risperidone and Clozapine) used in psychosis, agitation, anxiety and as mood stabilizers

• Benzodiazepines for sleep disturbances, anxiety and agitation in psychiatry.

Discontinuation syndrome can occur with different agents, including opiates, beta- blockers and more for the purpose of this article, we will focus on the first three items. If we look at the numbers, up to 30% of the population may need one of these 3 classes for depression, schizophrenia or bipolar in their lifetime. For all intents and purposes, an agent that has physiological or psychological effects may result in patients experiencing discontinuation syndrome. however, certain agents are more susceptible to producing discontinuation syndrome. These are agents with very short half-lives, no active metabolites, dosed at high levels or agents that are used for a protracted period.

Physiological dependence on these medications is a normal consequence of pharmacological receptor site activity. Receptors that may be involved with the TCA agents (e.g. imipramine) can be explained by adrenergic overdrive or cholinergic overdrive. In adrenergic overdrive, TCA’s inhibit NE uptake, increasing synaptic NE concentrations. Alpha2 receptor stimulation occurs via negative feedback resulting in decreased adrenergic firing. So prolonged TCA use causes blunting of this loop and thus when TCA’s are discontinued, the negative feedback loop inhibits adrenergic firing. In cholinergic overdrive, TCA bind to muscarinic receptors cebtrally and peripherally, leading to muscarinic up regulation. When the TCA is abruptly stopped, there are cholinergic symptoms from cholinergic hyperactivity.

Antidepressant DS may occur with tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and SSRIs. Symptoms usually start within a few days at most of treatment cessation, or rarely, when tapering down a dosage. Distinguishing antidepressant DS from the underlying depression is important. DS symptoms usually present within one day to three days, whereas depressive symptoms usually only present two weeks to three weeks after antidepressant medication is stopped. DS usually subsides in a few days, especially if antidepressant treatment is re-started. Up to 30% of patients who stop SSRI treatment will experience DS.

Proposed mechanisms with the SSRI agents include that there is an increased concentration of serotonin in the synapse. This then results in a desensitization of the postsynaptic serotonin receptor by down regulation. When the agents are discontinued, there is a temporary deficiency of serotonin in the synapse, which leads to the physical symptoms.

With the antipsychotics, DS was first identified in the late 1950’s with chlorpromazine when it was being trailed as an anti-TB agent. The DS occurred in 5/17 subjects. Most atypical agents have some serotonin-dopamergic antagonism and there are now case reports for all of the atypical agents. The proposed mechanism of action is that there is weak dopamine D2 antagonism and potent serotoninergic (5HT2) antagonism. Also they inherently have effects (antagonism) at the alpha-adrenergic, histaminergic and cholinergic receptors, the ratio depending on the individual agent. Thus, we see a rebound from these receptors when the agent is stopped. This also explains why the atypicals have a very specific DS for each different agent.

In benzodiazepines, they modulate the neurotransmitter activity of GABA and interact with binding sites on the GABA receptor complex. This results in an increased receptor affinity for GABA. When the benzodiazepine is stopped, there are decreased GABA binding sites/ inhibitory effects and the increased glutamate, which yield the excitatory effects. Chronic use of benzodiazepines leads to adaptive changes, including GABA receptor down regulation and increased glutamate. This contributes in part to the DS seen with benzodiazepines.

Given the fact that up to 25% of the population may have depression in their lifetime, 1-2% schizophrenia and 5-7% bipolar disorder, physicians involved in mental health care need to be aware of the main factors precipitating DS. These include risk factors may be directly related to higher doses, or usage for prolonged duration of time
As well as possibly a past history of substance abuse (8) considering the psychological “need” to continue with a medication. Additionally, by recognizing characteristic symptoms, avoiding abrupt discontinuation and providing adequate patient counseling and follow-up, physicians can play an active role in diminishing the occurrence of DS.
A helpful tool for practitioners to identify DS in patients is the acronym FINISH:

•F Fever

•I Insomnia

•N Nausea

•I Irritability

•S Sensory Changes

•H Headache

We must be aware that if a patient presents with signs and symptoms listed above, it is may be as a result of medication discontinuation. In general, the discontinuation syndrome signs and symptoms occur before the relapse of the Axis I disorder as the DS occurs within hours of drug discontinuation. Considering all of the factors such as patient diet, hydration and compliance are generally patient specific factors. Also, there are medication specific variables. These include concurrent medications that may affect metabolism, half-life of the medication and active metabolites. Other factors may be the patient’s dependence lability (psychological vs. physical withdrawal syndromes) and duration of therapy with the agent. One can determine if the symptoms that present are as a result of DS by simply introducing a low dose of the agent suspected. Signs and symptoms are ameliorated within a very short time period depending on the dose, concentration, Cmax and Tmax plus half-life of the agent.